The regulation of glycogen metabolism in C-6 astrocytoma cells and C-1300 neuroblastoma cells is being investigated. The active forms and the total activity of glycogen phosphorylase and glycogen synthase and the concentrations of intracellular glycogen, glucose, glucose 6-P, uridine diphosphoglucose and cyclic AMP have been measured. Two independent mechanisms serve to control glycogen metabolism in both the glioma and neuroblastoma cell lines; (1) both cell lines respond to fluctuations in available energy sources, in this case glucose, with changes in the active forms of the biosynthetic and degradative enzymes, and the intracellular glycogen concentration. When insulin is given, phosphorylase a is decreased, synthase a is increased and glucose transport into the cell is facilitated. (2) The administration of compounds which result in the elevation of the concentrations of intracellular cyclic AMP, cause an increase in phosphorylase a, a decrease in synthase a and a decrease in intracellular glycogen concentration. Norepinephrine and isobutylmethylxanthine (IBMX) are effective when given to C-6 astrocytoma cells. Prostaglandin 1E, and IBMX are effective when administered to C-1300 neuroblastoma cells in culture.